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Elevated levels of NO in both unchallenged and LPS‐challenged C. parvum ‐primed mice are attributable to the activity of a cytokine‐inducible isoform of iNOS
Author(s) -
Smith Sidney R.,
Manfra Denise,
Davies Liza,
Terminelli Carol,
Denhardt Georgette,
Donkin Jennifer
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.1.24
Subject(s) - lipopolysaccharide , biology , priming (agriculture) , nitric oxide , cytokine , corynebacterium parvum , tumor necrosis factor alpha , ratón , nitric oxide synthase , endocrinology , microbiology and biotechnology , immunology , medicine , botany , germination
Elevated levels of nitric oxide (NO 2 ‐ /NO 3 ‐ ) were detected in the serum of mice 3–7 days after priming with Corynebacterium parvum ( Propiombacterium acnes ). The serum NO 2 ‐ /NO 3 ‐ response was completely inhibited when C . parvum ‐primed ( C. parvum ) mice were treated with N G ‐monomethyl‐l‐arginine (l‐NMMA) or aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited when the mice were treated with interleukin‐10 (IL‐10) and the cytokine was most effective when given in multiple doses beginning on the day of priming. In contrast to l‐NMMA and AG, IL‐10 had no effect on the serum NO 2 ‐ /NO 3 ‐ response when administered to the mice on days 6 and 7 post priming. The inducible isoform of NOS (iNOS) appeared to be responsible for the elevated NO 2 ‐ /NO 3 ‐ response in C. parvum mice because iNOS transcripts were readily detected in their livers. Moreover, these transcripts as well as the circulating levels of NO 2 ‐ /NO 3 ‐ were dramatically reduced when the mice were treated with anti‐tumor necrosis factor α (anti‐TNF‐α) or antiinterferon‐γ (anti‐IFN‐γ) monoclonal antibodies (mAbs) during the priming interval. There was a modest increase (less than twofold) in the serum NO 2 ‐ /NO 3 ‐ response following a lipopolysaccharide (LPS) challenge to C. parvum mice (C. parvum/ LPS mice). LPS had a more dramatic stimulatory effect if the levels of NO 2 ‐ /NO 3 ‐ preexisting in C. parvum/ LPS mice were reduced by treatment with l‐NMMA, AG, or IL‐10 before the challenge. Thus the levels of NO 2 ‐ /NO 3 ‐ that preexisted in C. parvum/ LPS mice appeared to influence their ability to mount a NO 2 ‐ /NO 3 ‐ response subsequent to the LPS challenge. The NO 2 ‐ / NO 3 ‐ response did not contribute to lethality in C . parvum/ LPS mice because anti‐TNF‐α and anti‐IFN‐γ mAbs were protective but had no effect on serum NO 2 ‐ /NO 3 ‐ levels when administered to mice 24 h before the LPS challenge. J. Leukoc. Biol . 61:24–32; 1997.